Method and apparatus for noninvasive measurement of blood glucose by photoacoustics

ABSTRACT

A method and apparatus for noninvasively measuring blood glucose levels provides an indirect, reagentless, differential, photoacoustic technique which responds to absorption in a thin surface layer. An excitation source provides electromagnetic energy which is utilized to irradiate the tissue, such as skin. The output of the radiation of the excitation source at the desired wavelength is coupled through a transmission device, such as a fiber optic bundle, which irradiates the electromagnetic energy onto the body surface. Upon irradiation, acoustic energy is generated by the absorption of the electromagnetic energy in a relatively thin layer of the sample to be measured, characterized by a heat-diffusing length. The acoustic energy is detected by the probe which includes a measuring cell, reference cell, window and differential microphone. Absorption of the light beam results in periodic heating of the tissue, at and near the tissue surface. The air in contact with the tissue surface in the measuring cell is in turn heated, and produces an acoustic emission in the measuring cell. This acoustic emission is detected with the differential microphone, one end of which is positioned in the measuring cell and the other end of which is positioned in the reference cell. A processor determines the concentration of the substance based upon the detected acoustic signal.

BACKGROUND OF THE INVENTION

The present invention relates generally to measurement devices, and moreparticularly to noninvasive measurement of blood glucose byphotoacoustics.

An estimated 16 million Americans (approximately 7% of the totalpopulation in the United States) have diabetes, a disease which cancause severe damage to the heart, kidneys, eyes and nerves. Diabeticsneed to monitor their blood glucose levels frequently, often as much assix times a day, to maintain a proper level of insulin in their blood.Intense testing and treatment of diabetes can reduce the complications,including blindness, kidney failure and heart attack, by as much as 70%.

A well-known invasive procedure for monitoring blood glucose levelsinvolves pricking the finger of a patient to obtain a blood sample, andanalyzing it for glucose content by the use of an enzyme-based method.This invasive method, which is painful and has risk of infection, oftenprevents the patient from performing the needed frequent testing andtreatment. Additionally, because finger-stick monitoring is anenzyme-based technique, the cost for this technique is high.

Techniques which rely on non-invasive monitoring of glucose generallyutilize infrared or near infrared technology to noninvasively obtainoptical signatures indicating the level of glucose. Some of theseinfrared techniques rely on direct photoacoustic generation methods fornoninvasive monitoring. In direct photoacoustic generation methods, theacoustic wave is produced in a sample where the excitation beam isabsorbed. For example, U.S. Pat. No. 5,348,002 to Caro discloses adevice for measuring blood glucose which includes a light source forapplying electromagnetic radiation to tissue under analysis and atransducer for detecting acoustic energy. The transducer is positionedon one side of the finger and the incoming electromagnetic wave impingeson the other side of the finger, opposite the transducer. This techniqueis generally unreliable because a tissue, such as a body part, isoptically thick. The impinging electromagnetic energy is almost totallyabsorbed by the tissue. Consequently, the measured acoustic wave willrespond to the total incident electromagnetic energy--not just thefraction absorbed by glucose.

The technique disclosed in Caro also fails to compensate for the adverseeffects caused by the absorption of radiation by water, rather than themedium to be measured, such as glucose. The effect of strong waterabsorption is twofold. First, because tissue has a high percentage ofwater, water absorption can prevent a light beam from penetrating asufficient depth through tissue. Second, water absorption can yield anacoustic signal which is overwhelming compared to that from glucose. Inparticular, when electromagnetic energy impinges on water at certainwavelengths, the water optically absorbs the electromagnetic energy,inducing a temperature rise and related pressure variations in thetissue. The pressure changes caused by water are transmitted to thetransducer as a series of pulses or waves, thus overwhelminglyinterfering with the measurement of glucose.

Another photoacoustic method for direct, non-invasive monitoring ofglucose which also fails to address the adverse effects caused by theabsorption of radiation by water is described in EP 0 282 234, whichdiscloses a technique for measuring blood glucose utilizing a transducerfor monitoring acoustic energy. In EP 0 282 234, a semiconductor laseroperating in the wavelength range of about 1300 to 1580 nm is utilizedto excite glucose in a blood stream to generate acoustic energy. At thiswavelength range, water absorption can adversely affect glucosemeasurements. As with other direct photoacoustic techniques, foraccurate measurements, the medium must be optically thin. Unfortunately,most tissue in any body part is optically thick.

Other recent noninvasive devices for monitoring blood glucose sufferfrom shortcomings as well. One such device, referred to as the "DreamBeam", developed by Futrex Medical Instrumentation, Inc. ofGaithersburg, Maryland and disclosed in U.S. Pat. Nos. 5,028,787,5,077,376 and 5,576,544, includes a battery-operated box about the sizeof a television remote control designed to provide noninvasive glucosemeasurements with the use of infrared radiation. Infrared light, havinga wavelength between about 600 and 1000 nm, is passed through a finger.This approach has failed to produce accurate measurements as well.

Another noninvasive device, referred to as the "Diasensor 1000",developed by Biocontrol Technology, Inc. of Pittsburgh, Pa. anddisclosed in U.S. Pat. No. 5,070,874, has failed to produce accurateresults as well. In this device, a tabletop spectrophometer is designedto recognize a person's glucose patterns through the use of a light beamthat passes through the skin of the forearm into the blood and is thenreflected back to a sensor. A microprocessor is intended to interpretthe data and calculate the blood glucose level. This reflectiontechnique suffers from numerous shortcomings, including a small returnsignal, scattering from tissue (which reduces the signal and increasesfluctuation) and interferences by strong background light.

As of date, no noninvasive glucose monitors, including the devicesdiscussed above, have been approved by the Federal Drug Administration.This is mainly because current methods, which rely in large part onoptical transmission or reflection, generally do not have sufficientsensitivity. In particular, absorption by glucose molecules is extremelyweak compared to other blood constituents. Consequently, the returnsignal which is generated by other blood constituents is overwhelmingcompared to that by glucose, resulting in inaccurate measurements.Additionally, these optical techniques are severely limited by noiseinduced by light scattering through the tissue and cell walls. Asophisticated chemometric data process algorithm is often required tosuppress such noise.

What is needed therefore is an apparatus and method for monitoring bloodglucose which is painless, noninvasive, accurate and economical.

SUMMARY OF THE INVENTION

The preceding and other shortcomings of the prior art are addressed andovercome by the present invention which provides an apparatus fordetermining a concentration of a component in a first medium, includinga source for irradiating a portion of the first medium by heat-diffusionto generate acoustic energy propagating in a second medium over asurface of the first medium in response to the irradiation, a detectorfor detecting the acoustic energy and providing an acoustic signal inresponse to the acoustic energy and a processor for determining theconcentration of the component in response to the acoustic signal andcharacteristics of the component.

In another aspect, the present invention provides a method fordetermining a concentration of a component in a first medium, includingthe steps of irradiating a portion of the first medium by heat-diffusionto generate acoustic energy propagating in a second medium over asurface of the first medium in response to the irradiation, detectingthe acoustic energy and providing an acoustic signal in response to theacoustic energy and determining the concentration of the component inresponse to the acoustic signal and characteristics of the component.

In still another aspect, the present invention provides an apparatus formeasuring a concentration of an analyte in a first medium, including asource for providing electromagnetic energy at wavelengths correspondingto the absorption characteristics of the analyte to excite a portion ofthe first medium by heat-diffusion to generate acoustic energypropagating in a second medium in response to the excitation, a detectorfor detecting the acoustic energy and providing an acoustic signal inresponse to the acoustic energy and a processor for determining theconcentration in response to the acoustic signal and absorption spectrumof the analyte.

In a further aspect, the present invention provides a method formeasuring a concentration of an analyte in a first medium, including thesteps of providing electromagnetic energy at wavelengths correspondingto the absorption characteristics of the analyte to excite a portion ofthe first medium by heat-diffusion to generate acoustic energypropagating in a second medium in response to the excitation, detectingthe acoustic energy and providing an acoustic signal in response to theacoustic energy and determining the concentration in response to theacoustic signal and absorption spectrum of the analyte.

In another aspect, the present invention provides an apparatus fordetermining a concentration of glucose in a body part, including asource for irradiating a portion of the body part by heat-diffusion togenerate acoustic energy propagating in air over a surface of the bodypart in response to the irradiation, a detector for detecting theacoustic energy and providing an acoustic signal in response to theacoustic energy and a processor for determining the concentration ofglucose in response to the acoustic signal and characteristics ofglucose.

In a further aspect, the present invention provides a method fordetermining a concentration of glucose in a body part, including thesteps of irradiating a portion of the body part by heat-diffusion togenerate acoustic energy propagating in air over a surface of the bodypart in response to the irradiation, detecting the acoustic energy andproviding an acoustic signal in response to the acoustic energy anddetermining the concentration of glucose in response to the acousticsignal and characteristics of glucose.

The foregoing and additional features and advantages of this inventionwill become apparent from the detailed description and accompanyingdrawing figures below. In the figures and the written description,numerals indicate the various features of the invention, like numeralsreferring to like features throughout for both the drawing figures andthe written description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagram of a noninvasive photoacoustic measurement device inaccordance with a preferred embodiment of the present invention;

FIG. 2 is a detailed diagram of the probe illustrated in FIG. 1;

FIG. 3 is a graph showing the absorption spectrum of glucose derivedfrom a 0.75-M glucose/water solution;

FIG. 4 is a graph showing the absorption spectrum of water;

FIG. 5 is a graph showing estimated percentage changes in absorption ofa 100 mg/dl glucose/water solution over water;

FIG. 6 is a diagram showing a laboratory arrangement for noninvasivephotoacoustic measurements of glucose in a glucose/water solution;

FIG. 7 is a graph showing a photoacoustic spectra of a saturatedglucose/water solution and of water, generated from the measurementdevice illustrated in FIG. 6; and

FIG. 8 is a graph showing the percentage increase in the normalizedacoustic intensity of glucose over water versus glucose concentrationfor various laser wavelengths.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Referring to FIG. 1, a noninvasive photoacoustic system 10 for measuringa concentration of a sample is illustrated. The noninvasivephotoacoustic system 10 of the present invention is preferably utilizedto measure blood glucose levels and provides an indirect, reagentless,differential, photoacoustic technique which responds to absorption in athin surface layer. In particular, in the present invention, onlyabsorption in a relatively thin layer of the sample to be measured,characterized by a heat-diffusing length, is responsible for generationof an acoustic emission. The indirect photoacoustic system 10 of thepresent invention can thus be used to probe the absorption of a sampleeven under optically thick conditions.

The present invention is not limited to the measurement of blood glucoselevels, but may also be utilized to measure the concentration of othersubstances or analytes, particularly those in human body tissue. Forexample, the present invention can be utilized to monitor adenosinetriphosphate, blood alcohol, blood gas, hemoglobin, cholesterol andvarious ions in blood streams, and drugs of abuse.

As is illustrated in FIGS. 1 and 2, the photoacoustic system 10 includesan excitation source 12, controller/modulator 14, probe 16, lock-inamplifier 18 and processor 20 for measuring the concentration of asample, such as glucose. The excitation source provides electromagneticenergy which is utilized to irradiate the tissue, such as skin. Theoutput of the radiation of the excitation source 12 at the desiredwavelength is coupled through a transmission device 22, such as a fiberoptic bundle, which irradiates the electromagnetic energy onto the bodysurface 24. The present invention is not limited to utilization of thetransmission device 22. Rather, the output of the radiation of theexcitation source 12 can be transmitted directly to the body surface 24or indirectly through the transmission device 22. For illustrativepurposes, however, a transmission device 22 in the form of a fiber opticbundle will be utilized. Upon irradiation, acoustic energy is generatedby the absorption of the electromagnetic energy in a relatively thinlayer of the sample to be measured, characterized by a heat-diffusinglength as discussed in detail below.

As is illustrated in detail in FIG. 2, the acoustic energy is detectedby the probe 16 which includes a measuring cell 26, reference cell 28,window 30 and differential microphone 32. An acoustic wave is generatedin the measuring cell 26 by heat transfer from the thin layer ofirradiated tissue 24. In particular, the output of the radiation iscoupled through the transmission device 22, such as a fiber-opticbundle, which irradiates a sample, such as tissue. Absorption of thelight beam results in periodic heating of the tissue, at and near thetissue surface 24. The radiation is focused on the tissue surfacethrough the window 30 of the measuring cell 26. The measuring cell 26 isair-tight sealed on one end with the window 30 mounted over themeasuring cell opening. The window 30 is preferably manufactured from asuitable material selected for transmission of light from the excitationsource 12. Since the laser beam is modulated at certain frequencies, thetemperature of the tissue is also modulated at the same frequency in theregion where the laser beam is incident. The air 38 in contact with thetissue surface 24 in the measuring cell 26 is in turn heatedperiodically at the same modulated frequency. Because of this periodictemperature variation of the air in the measuring cell 26, the airexpands and contracts periodically, thus generating a periodicalacoustic wave at the same modulated frequency in the measuring cell 26.This acoustic wave is detected with the differential microphone 32, oneend 40 of which is positioned in the measuring cell 26 and the other end42 of which is positioned in the reference cell 28. Absorption of thelight in the air 38 itself is minimal, and therefore substantially allheating arises from absorption of the light in the thin layer ofirradiated tissue 24.

The measuring and reference cells 26 and 28 are preferably air cellswhich are closely-spaced to one another, typically having their outerrims positioned within 1 mm to 1 cm from each other, far enough apartsuch that radiation will not diffuse from one cell to the other. Theends 40 and 42 of the measuring and reference cells 26 and 28,respectively, are formed by the surface 24 of a body part. The rims ofthe cells 26 and 28 are preferably pressed to the body surface 24 toform substantially sealed spaces within each respective cell 26 and 28.The differential cells 26 and 28 prevent overloading of the lock-inamplifier 18 from bodily noise, typically generated from muscle spasmsand/or pulsative bloodflow through subcutaneous vessels. Each cell 26and 28 has its acoustic outlet 40 and 42, respectively, connected with asound port of the differential microphone 32 which measures thedifference in acoustic response from the two closely-spaced cells 26 and28 as they are pressed against the body surface 24. A photoacousticsignal is generated in the measuring cell 26 by irradiation of the bodysurface 24. In operation, the measuring cell 26 is thus, uponirradiation of the body surface 24, positioned over a laser irradiatedbody surface 46 and the reference cell 28 is positioned over a non-laserirradiated body surface 48. Bodily noise, which may at times begenerated in both cells 26 and 28, is suppressed by the differentialmicrophone 32. In particular, the noise signals from both the measuringand reference cells 26 and 28, typically almost the same with respect tomagnitude and phase, are canceled out by the differential microphone 32.The differential microphone 32 thus separates the acoustic signal fromthe background noise.

The detected signals from the probe 16 are then applied to the lock-inamplifier 18 which records and averages the output signal from thedifferential microphone 32. The lock-in amplifier 18 also extracts fromthe output signal only those signals which have the same frequencycomponent as the modulation frequency of the irradiated light generatedby the excitation source 12 under the control of thecontroller/modulator 14. The frequency component extracted is thenapplied to processor 20, typically a microprocessor data acquisitionsystem. The processor 20 may implement a frequency domain analysis toanalyze the temporal frequency response of the extracted acoustic signalin order to improve the signal to noise ratio. A chemometric spectralanalysis technique may also be utilized to deduce the observedphotoacoustic spectrum to improve the detection limit and accuracy.

The photoacoustic system 10 of the present invention measures glucosewithin a characteristic heat-diffusion length from the surface 24 of amedium, such as a body part i.e. skin. The heat diffusion length isdefined in accordance with the following equation:

    ______________________________________                                        Diffusion length =                                                                       (D/πf).sup.0.5       (1)                                        where D =  thermal diffusivity (cm.sup.2 /s)                                  f =        modulation frequency of excitation source (Hz)                     π =     3.14159265 (constant)                                              ______________________________________                                    

Diffusivity (D) is defined in accordance with the following equation:

    ______________________________________                                        D =        k/(ρc)              (2)                                        where k =  thermal conductivity (cal/cm-s-° C.)                        c =        heat capacity of the material (cal/g-° C.)                  ρ =    density of the material (g/cm.sup.3)                               ______________________________________                                    

For example, according to equation (2), assuming a heat capacity (c) of0.8 cal/g-°C. and a thermal conductivity (k) of 0.0015±0.003cal/cm-s-°C. at 23-25° C., the diffusivity (D) of a typical skin wouldbe about 7×10⁻⁴ cm² /s. According to equation (1 ), for a thermaldiffusivity (D) of about 7×10⁻⁴ cm ² /s for a typical skin and a diodelaser having a modulation frequency (f) of 1 Hz, the heat diffusionlength of a typical skin would be about 150 μm. Thus, a diffusion lengthof about 100 to 200 μm can be achieved with a suitable selection of thefrequency of the irradiated light.

The present invention is thus particularly useful for monitoring inthose areas of the body in which the stratum corneum is relatively thinand glucose can be accessed within the thin layer below the tissuesurface. The inner lip is a preferred body part because its mucosalmembrane is relatively thin, typically in the range of about 50-100 μm.Glucose in interstitial fluid or capillary blood vessels beneath themucosal membrane can thus be accessed within about 100 to 200 μm of anestimated diffusion length as discussed above. Since glucose ininterstitial fluid is generally equilibrated well with that in blood,the present invention may be utilized to measure glucose in theinterstitial fluid as well as in the capillary blood vessels.

The present invention is relatively immune to turbid conditions. Inparticular, although the incident light may be diffused by scatteringmediums, such as red blood cells, tissue and blood vessel walls, theoptical absorption process continues as does the photoacousticgeneration. Although the presence of scatter may increase the radius ofthe interactive region, the photoacoustic response should remain nearlythe same. This is particularly important since biological tissue is amedium which tends to highly scatter light.

The excitation source 12 is preferably operable at wavelengths whichcoincide with the wavelengths where absorption of the substance to bemeasured is relatively strong and the absorption of any interferingsubstances, such as water, is relatively weak. For example, referring tothe graph 34 in FIG. 3, for determining the concentration of glucose ina bloodstream, the excitation source 12 is preferably tuned to theabsorption bands of glucose in the spectral ranges from about 1520-1850nm and about 2050-2340 nm to induce a strong photoacoustic emission. Inthese wavelength ranges, water absorption is relatively weak and glucoseabsorption is relatively strong. Thus, in accordance with the presentinvention, even though tissue may have a high percentage of water, atthe above-specified wavelength regions, the electromagnetic radiation isable to penetrate through the tissue to a sufficient depth to allow foraccurate measurements. Despite water absorption, the acoustic signalwhich is generated by the absorption of electromagnetic radiation byglucose is not overwhelmed by that generated by water. In particular,when electromagnetic energy impinges on glucose at the above-specifiedwavelengths, the glucose optically absorbs the energy, inducing atemperature rise and generating an acoustic emission indirectly in theair. The acoustic emission caused by the glucose is transmitted to themicrophone as a series of pulses or waves.

Referring to FIG. 1, the excitation source 12 may be a plurality oflaser diodes. A laser diode is generally preferable due to its compactsize and low cost. Since the tunable wavelength range of a diode lasermay not be large enough to accommodate the desired wavelength ranges ofoperability, in some cases, such as for the measurement of theconcentration of glucose, a plurality of laser diodes each havingvariable tunable wavelengths may be utilized to generate electromagneticenergy to correspond with the wavelength regions where absorption isstrongest. In such case, the resulting beam from the diodes is delivereddirectly or through the transmission device 22, such as a fiber opticbundle, to irradiate the body surface 24 as shown in FIG. 2. Thetransmission device 22 is not limited to a fiber optic bundle, butrather may be any waveguide which enables the electromagnetic radiationgenerated by the excitation source 12 to be reliably transmitted to thebody surface 24.

Additionally, the present invention is not limited to the use of one ormore diode lasers as the excitation source 12. Rather, the presentinvention may take advantage of conventional or newly-developed coherentand non-coherent light sources as well as solid-state devices. Suchknown sources include, but are not limited to, light emitting diodes(LED), optical parametric oscillator lasers (OPO), Fourier TransformedInfrared (FTIR) based light sources and other noncoherent light sourcessuch as heated wires and lamps. OPO lasers are discussed in "OpticalParametric Oscillators", Laser Handbook, by E. Smith, F. T. Arecchi andE.O. Schultz-Dubois (North Holland Amsterdam, 1972), volume 1, pages837-895. FTIR based continuous light sources are discussed in"Quantitative Depth Profiling of Layered Samples Using Phase-ModulationFT-IR Photoacoustic Spectroscopy", by Roger W. Jones and John F.McClelland, Applied Spectroscopy, Volume 50, Number 10, 1996. As withthe use of a plurality of diode lasers, it may be desirable to use oneor more light sources in combination to produce the desired spectrum ofwavelengths.

The examples provided herein are to illustrate specific instances of thepractice of the invention and are not to be construed as limiting thepresent invention to these examples.

Referring to FIG. 3, a graph 34 of the absorption spectrum of glucosederived from a 0.75-M (or 13.5 g/dl) glucose/water solution isillustrated. The absorption spectrum of glucose was measured in order todetermine suitable laser wavelengths for glucose measurements. Inparticular, a Fourier Transform Infrared (FTIR) spectrometer, in thiscase a Galaxy Model 7600 by Mattson Instruments of Madison, Wisconsin,with a spectral resolution of 2 cm⁻¹, was used to measure the absorptionspectrum of a glucose/water solution in a 0.5-mm-pathlength cell. Theabsorption spectrum of glucose illustrated in FIG. 3 was derived bysubtracting the absorbance of water alone from that of the glucosesolution. The two relatively strong peaks 46 and 48 of glucoseabsorption are at about 1600 and 2120 nm, and the two weaker peaks 50and 52 are at about 2270 and 2320 nm.

Referring to FIG. 4, a graph 54 of the absorption spectrum of water isillustrated. The glucose absorption peaks, shown in FIG. 3, fall withinthe water absorption transmission windows. Even in the watertransmission windows, absorption by water is much stronger than that byglucose in the concentration range of interest. Based on FIG. 4, theabsorption depth of water 56 and 68 is about 0.57 and 4.8 mm at about2120 and 1600 nm, respectively. The absorption depth is defined as thedistance at which the incident light is reduced by 1/e (where e=the baseof the system of natural logarithms having the approximate numericalvalue 2.71828). As long as the absorption depth is larger than theestimated heat diffusing length, effective measurements can be made.

Referring to FIG. 5, a graph 60 of the percentage change in absorptionof a 100 mg/dl glucose/water solution, as estimated from that at a 7.5-Mglucose/water solution shown in FIG. 3, over that of water alone (FIG.4), is illustrated. The positive value indicates increase in absorptiondue to the presence of glucose. The negative value indicates decrease inwater absorption due to substitution of water molecules by glucose. Theincrease reaches a maximum 62 of about 0.12% at 1600 nm and anothermaximum 64 of about 0.057% at 2120 nm. Referring to FIGS. 3 and 5,although the absorption peak 48 at 2120 nm for glucose is stronger thanthe absorption peak 46 at 1600 nm, the absorption peak 46 at 1600 nmpeak may yield a higher sensitivity because of the higher percentage 62(by about a factor of 2.1) over water absorption as shown in FIG. 5.

One skilled in the art will recognize that the present invention isdirected towards providing an indirect, photoacoustic technique whichresponds to absorption in a thin surface layer and is not limited to theconfiguration illustrated in FIG. 1. In particular, in accordance withanother embodiment of the invention, the present invention may beadapted to be utilized with a microphone positioned above the surfacefor detecting the acoustic wave. Additionally, the present invention isnot limited to the use of a lock-in amplifier for extracting thedetected acoustic signal from interfering signals, such as backgroundnoise signals. Rather, a digital oscilloscope or other data acquisitiondevices may be utilized to average the acoustic signal and thendifferentiate it from any interfering signals.

In operation, the present invention may be utilized to providephotoacoustic measurements of glucose/water solutions at various glucoseconcentrations, as illustrated in the laboratory arrangement of thepresent invention 66 shown in FIG. 6. A Co:Mg:F₂ laser 68 by SchwartzElectro-Optics, Inc. of Orlando, Fla., provides an output wavelengthtunable from about 1900 to 2500 nm was utilized as the excitationsource. The laser 68, which is pulsed at about 1 Hz, is directed by atuning mirror 70 and then focused by a lens 72 into a glucose/watersolution 74 in a 50-ml glass beaker. A microphone 76, positioned in theair above the glucose/water solution 74, is used to monitor theresulting acoustic wave 78, generated indirectly as discussed above. Theoutput from the microphone 76 is applied to a preamplifier 94 foramplification. The amplified signal is then applied to a recorder 80, inthis case a digital oscilloscope by Tektronix of Wilsonville, Oreg., forrecordation and averaging for about 20 pulses at each wavelengthsetting.

Results of the measurements made by the present laboratory arrangement66 are illustrated in the graph 82 shown in FIG. 7. The acousticintensity is given as I/E, where I is the peak of the acoustic intensityand E is the incident laser energy. Glucose has a relatively broad andstrong peak 84 at about 2120 nm, and two weaker peaks 86 and 88 at about2270 and 2320 nm, respectively. These peaks 84, 86 and 88 are consistentwith that expected from the glucose absorption spectrum as shown in FIG.3. The present invention can thus be utilized to measure glucose evenunder an optically thick condition.

FIG. 8 is a graph 90 showing the percentage increase in the normalizedphotoacoustic intensity of glucose over water versus glucoseconcentration for various excitation wavelengths. The photoacousticintensity is approximately linearly proportional to the glucoseconcentration over a 20-fold variation in concentration. The increase inphotoacoustic intensity 92 over water is about 7.7% at about 4000 mg/dlfor an excitation wavelength of 2147 nm.

The present experimental arrangement, without aid from a data-analysisalgorithm, demonstrated the ability to measure the glucose concentrationto about 200 mg/dl. The detection sensitivity can be improved by afactor of about 2.1 by switching to an excitation wavelength ofapproximately 1600 nm, as shown in FIG. 5. Furthermore, any experimentalerror shown in FIG. 8 is caused mainly by the variation in the laserpulse energy. Pulse-to-pulse variation in the current Co:MgF₂ laser isquite high, about 10 to 20%. The measurement sensitivity can be furtherimproved substantially by use of a more stable laser. A diode laser isknown to be very stable with fluctuation of less than about 0.1% over along period of several tens of minutes. By extrapolating the preliminarydata to what can be expected with a diode laser at about 1600 nm, thehigh sensitivity needed for a physiological concentration range ofinterest, from about 30 to 400 mg/dl, can be achievable.

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been shown and describedhereinabove, nor the dimensions of sizes of the physical implementationdescribed immediately above. The scope of invention is limited solely bythe claims which follow.

What is claimed is:
 1. An apparatus for determining a concentration of acomponent in a first medium, comprising;a source for irradiating aportion of said first medium by heat-diffusion to generate acousticenergy propagating in a second medium over a surface of said firstmedium in response to said irradiation; a detector for detecting saidacoustic energy and providing an acoustic signal in response to saidacoustic energy, said detector comprising a differential microphone forconverting said acoustic energy to said acoustic signal disposedexternally of said first medium and in contact relation with said secondmedium for detecting said acoustic energy; and a processor fordetermining the concentration of said component in response to saidacoustic signal and characteristics of said component.
 2. The apparatusclaimed in claim 1, wherein said detector for detecting said acousticenergy and providing an acoustic signal in response to said acousticenergy, further comprises:a first cell adapted to be disposed in contactrelation with said irradiated portion of said first medium and connectedto said differential microphone; and a second cell adapted to bedisposed in contact relation with said first medium, adjacent to saidirradiated portion, and connected to said differential microphone,wherein said acoustic energy is generated in said first cell due toaffect of irradiation on said first medium.
 3. A method for determininga concentration of a component in a first medium, comprising the stepsof:irradiating a portion of said first medium by heat-diffusion togenerate acoustic energy propagating in a second medium over a surfaceof said first medium in response to said irradiation; detecting saidacoustic energy and providing an acoustic signal in response to saidacoustic energy by converting said acoustic energy to said acousticsignal utilizing a device disposed externally of said first medium andin contact relation with said second medium for detecting said acousticenergy and differentiating said acoustic signal from background signals;and determining the concentration of said component in response to saidacoustic signal and characteristics of said component.
 4. The methodclaimed in claim 3, wherein said step of detecting said acoustic energyand providing an acoustic signal in response to said acoustic energy,further comprises the steps of:determining a first acoustic response ina first cell disposed in contact relation with said irradiated portionof said first medium; determining a second acoustic response in a secondcell disposed in contact relation with said first medium, adjacent tosaid irradiated portion; and differentiating said first and secondacoustic responses to generate said acoustic signal.
 5. An apparatus formeasuring a concentration of an analyte in a first medium,comprising:means for providing electromagnetic energy at wavelengthscorresponding to the absorption characteristics of said analyte toexcite a portion of said first medium by heat-diffusion to generateacoustic energy propagating in a second medium in response to saidexcitation; means for detecting said acoustic energy and providing anacoustic signal in response to said acoustic energy, comprising:adifferential microphone; a first cell adapted to be disposed in contactrelation with said irradiated portion of said first medium and connectedto said differential microphone; and a second cell adapted to bedisposed in contact relation with said first medium, adjacent to saidirradiated portion, and connected to said differential microphone,wherein said acoustic energy is generated in said first cell due toexpansion and contraction of said second medium in response to saidelectromagnetic energy; and means for determining said concentration inresponse to said acoustic signal and absorption spectrum of saidanalyte.
 6. The apparatus claimed in claim 5, wherein said means fordetermining said concentration in response to said acoustic signal andabsorption spectrum of said analyte, further comprises:means forgenerating a photoacoustic spectrum of said analyte.
 7. A method formeasuring a concentration of an analyte in a first medium, comprisingthe steps of:providing electromagnetic energy at wavelengthscorresponding to the absorbing characteristics of said analyte to excitea portion of said first medium by heat-diffusion to generate acousticenergy propagating in a second medium in response to said excitation;detecting said acoustic energy and providing an acoustic signal inresponse to said acoustic energy, comprising the steps of:generating afirst acoustic response in a first cell disposed in contact relationwith said irradiated portion of said first medium and connected to saiddifferential microphone; generating a second acoustic response in asecond cell disposed in contact relation with said first medium,adjacent to said irradiated portion, and connected to said differentialmicrophone; and applying said first and second acoustic responses to adifferential microphone to generate said acoustic signal; anddetermining said concentration in response to said acoustic signal andabsorption spectrum of said analyte.
 8. An apparatus for determining aconcentration of glucose in a body part, comprising;a source forirradiating a portion of said body part by heat-diffusion to generateacoustic energy propagating in air over a surface of said body part inresponse to said irradiation; a detector for detecting said acousticenergy and providing an acoustic signal in response to said acousticenergy, said detector comprising a differential microphone forconverting said acoustic energy to said acoustic signal disposedexternally of said body part and in contact relation with said air fordetecting said acoustic energy; and a processor for determining theconcentration of said glucose in response to said acoustic signal andcharacteristics of said glucose.
 9. The apparatus claimed in claim 8,wherein said detector for detecting said acoustic energy and providingan acoustic signal in response to said acoustic energy, furthercomprises:a first cell adapted to be disposed in contact relation withsaid irradiated portion of said body part and connected to saiddifferential microphone; and a second cell adapted to be disposed incontact relation with said body part, adjacent to said irradiatedportion, and connected to said differential microphone, wherein saidacoustic energy is generated in said first cell due to affect ofirradiation on said body part.
 10. A method for determining aconcentration of glucose in a body part, comprising the stepsof:irradiating a portion of said body part by heat-diffusion to generateacoustic energy propagating in air over a surface of said body part inresponse to said irradiation; detecting said acoustic energy andproviding an acoustic signal in response to said acoustic energy byconverting said acoustic energy to said acoustic signal utilizing adevice disposed externally of said body part and in contact relationwith said air for detecting said acoustic energy and differentiatingsaid acoustic signal from background signals; and determining theconcentration of said glucose in response to said acoustic signal andcharacteristics of said glucose.
 11. The method claimed in claim 10,wherein said step of detecting said acoustic energy and providing anacoustic signal in response to said acoustic energy, further comprisesthe steps of:determining a first acoustic response in a first celladapted to be disposed in contract relation with said irradiated portionof said body part; determining a second acoustic response in a secondcell adapted to be disposed in contact relation with said body part,adjacent to said irradiated portion; and differentiating said first andsecond acoustic responses to generate said acoustic signal.